PROJECT SUMMARY Objectives: The purpose and objectives of the training program proposed for continued support remains to prepare bioengineers for an academic career in orthopaedic research as part of a broad program leading to the Ph.D. degree in Bioengineering. Training orthopaedic surgeons and bioengineers side-by-side in the same laboratory, together with life scientists at various levels of training, will continue to foster an environment conducive to research and education in the orthopaedic arena. Indeed, this has been the formula that we have found very successful in our training program thus far. Research areas represent a wide range of musculoskeletal problems including, but not limited to, the cellular and molecular biology of bone growth, repair, ossification, and maintenance; the etiology and pathogenesis of tendon and ligament injury, repair, and regeneration; factors for disc degeneration and restoration; biomimetic scaffolds; and functional tissue engineering. In addition to formal didactic coursework, training opportunities include a seminar series and journal club. Trainees: Four predoctoral positions are proposed to continue the success we have had in training them for academic careers. They will be training toward a Ph.D. degree in orthopaedic bioengineering which is typically five years in duration, though typically only two years will be supported by this training grant so that positions can be made available for new trainees to grow the program. Training Facilities: The primary facility is the McKay Orthopaedic Research Laboratory of the Department of Orthopaedic Surgery at the University of Pennsylvania. The multidisciplinary McKay Laboratory includes state-of-the-art facilities in Biochemistry, Bioengineering, Biophysics, Computation, Histology, Machine Shop, Molecular Biology, Specimen Preparation, and Cell and Tissue Culture. In addition, extensive laboratories throughout the Penn campus such as those of the Department of Bioengineering are available to the trainees. RELEVANCE This program will train orthopaedic bioengineers in fundamental research in order to position them for high-level academic careers, in which they will investigate important musculoskeletal problems and train the next generation of researchers.